The supportive therapies (e.g. antiemetics, premedications, etc.), infusion times, diluents, volumes and routes of administration, if included, are listed as defaults. They may vary between institutions and can be substituted to reflect individual institutional policy.

Antiemetics if included in the treatment schedule are based upon recommendations from national and international guidelines. These are defaults only and may be substituted to reflect individual institutional policy. Select here for recommended doses of alternative antiemetics.

The supportive therapies (e.g. antiemetics, premedications, etc.), infusion times, diluents, volumes and routes of administration, if included, are listed as defaults. They may vary between institutions and can be substituted to reflect individual institutional policy.

Antiemetics if included in the treatment schedule are based upon recommendations from national and international guidelines. These are defaults only and may be substituted to reflect individual institutional policy. Select here for recommended doses of alternative antiemetics.

Evidence for dose modifications is limited, and the recommendations made on eviQ are intended as a guide only. They are generally conservative with an emphasis on safety. Any dose modification should be based on clinical judgement, and the individual patient’s situation including but not limited to treatment intent (curative vs palliative), the antineoplastic regimen (single versus combination therapy versus chemotherapy versus immunotherapy), biology of the cancer (site, size, mutations, metastases), other treatment related side effects, additional co-morbidities, performance status and patient preferences.Suggested dose modifications are based on clinical trial findings, product information and reference committee consensus. Non-haematological gradings are based on Common Terminology Criteria for Adverse Events (CTCAE) unless otherwise specified. Renal and hepatic dose modifications have been standardised where possible. For more information see dosing considerations & disclaimer.

Note: all dose reductions are calculated as a percentage of the starting dose.

Delay treatment until toxicity has resolved to Grade 1 or less and reduce the dose for subsequent cycles as follows:
1st occurrence: No dose reduction
2nd occurrence: Reduce doxorubicin and cyclophosphamide by 25%
3rd occurrence: Reduce doxorubicin and cyclophosphamide by 50%
4th occurrence: Withhold chemotherapy

Grade 3 or Grade 4

Delay treatment until toxicity has resolved to Grade 1 or less and reduce the dose for subsequent cycles as follows:
1st occurrence: Reduce doxorubicin and cyclophosphamide by 50%
2nd occurrence: Withhold chemotherapy

Delay treatment until toxicity has resolved to Grade 1 or less and reduce the dose for subsequent cycles as follows:
1st occurrence: No dose reduction
2nd occurrence: Reduce doxorubicin and cyclophosphamide by 25%
3rd occurrence: Reduce doxorubicin and cyclophosphamide by 50%
4th occurrence: Withhold chemotherapy

Grade 3 or Grade 4

Delay treatment until toxicity has resolved to Grade 1 or less and reduce the dose for subsequent cycles as follows:
1st occurrence: Reduce doxorubicin and cyclophosphamide by 50%
2nd occurrence: Withhold chemotherapy

Increased effects/toxicity of dexamethasone due to inhibition of its metabolism via CYP3A4

Reduce dose of antiemetic dexamethasone by approximately 50% when adding a NK-1 antagonist. For protocols that already recommend a NK-1 antagonist, the dose reduction of antiemetic dexamethasone has already been taken into account.

If dexamethasone is part of the chemotherapy protocol, dose reduction as per the product information is not routinely recommended in clinical practice and no additional dexamethasone is required for antiemetic cover.

If concurrent use is unavoidable, monitor closely for efficacy/toxicity of both drugs.

Digoxin

Antineoplastic agents can damage the lining of the intestine; affecting the absorption of digoxin

Monitor digoxin serum levels; adjust digoxin dosage as appropriate

Antiepileptics

Both altered antiepileptic and antineoplastic levels may occur, possibly leading to loss of efficacy or toxicity

Where concurrent use of an enzyme-inducing antiepileptic cannot be avoided, monitor antiepileptic serum levels for toxicity, as well as seizure frequency for efficacy; adjust dosage as appropriate.
Also monitor closely for efficacy of the antineoplastic therapy

Diminished response to vaccines and increased risk of infection with live vaccines

Live vaccines (e.g. BCG, MMR, zoster and varicella) are contraindicated in patients on immunosuppressive therapy. Use with caution in patients on non-immunosuppressive therapy.
For more information; refer to the recommended schedule of vaccination for cancer patients, as outlined in the Australian Immunisation Handbook

Doxorubicin

ensure vein is patent and monitor for signs of extravasation throughout administration

flush with ~150 mL of sodium chloride 0.9%

potential for flare reaction during administration of doxorubicin (facial flushing and red streaking along the vein) stop infusion and exclude extravasation before continuing at a slower rate of infusion.

Discharge information

Antiemetics

Growth factor support

Patient information

The side effects listed below are not a complete list of all possible side effects for this treatment. Side effects are categorised into the approximate onset of presentation and should only be used as a guide.

Immediate (onset hours to days)

Extravasation, tissue or vein injury

The unintentional instillation or leakage of a drug or substance out of a blood vessel into surrounding tissue. This has the potential to cause damage to affected tissue.

Anthracycline flare reaction is caused by a localised allergic reaction. It is characterised by erythematous vein streaking, urticaria and pruritus which may occur during drug administration and is often associated with too rapid an infusion. Extravasation must be ruled out if flare occurs.

Erythematous and ulcerative lesions of the gastrointestinal tract (GIT). It commonly develops following chemotherapy, radiotherapy to the head, neck or oesophagus, and high dose chemotherapy followed by a blood and marrow transplant (BMT).

Irregular or absent periods, hot flushes, mood swings, sleep disturbance, night sweats, vaginal dryness, decreased libido and dyspareunia. This is caused by ovarian failure and may be temporary or permanent.

Cardiotoxicity

Anthracyclines are the most frequently implicated antineoplastic agents associated with cardiotoxicity, which typically manifests as a reduction in left ventricular ejection fraction (LVEF), cardiomyopathy, or symptomatic CHF. Anthracycline induced cardiotoxicity has been categorised into acute, early-onset chronic progressive and late-onset chronic progressive and is usually not reversible. The risk of clinical cardiotoxicity increases with a number of risk factors including higher total cumulative doses.

The evidence for this protocol comes from the trial CALGB 9741 by Citron et al, 2003. The study used a 2 X 2 factorial experimental design to assess the 2 factors of dose density (administering the drug every 2 weeks versus 3 weeks) and treatment sequence (concurrent vs sequential) and the possible interaction between them.r

A total of 2005 women were randomly assigned to receive one of the following 4 arms:

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Version 4

New format to allow for export of protocol information
Protocol version number changed to V.2
Antiemetics and premedications added to the treatment schedule
Additional Clinical Information, Key Prescribing table and Key Administration table combined into new section titled Clinical Considerations
Drug specific information placed behind the drug name link

07/04/2011

Monitoring - Test/Assessments added to Primary Health Care

27/04/2012

Protocol reviewed at Medical Oncology Reference Committee meeting. No changes and next review in 2 years.

30/01/2013

PHC/OMIS transfer completed

09/05/2014

Protocol reviewed by email survey. No change and next review in 2 years.
PHC view removed.

18/02/2016

Discussion with Medical Oncology Reference Committee Chairs and protocol to be reviewed every 5 years. Next review due in 3 years.

31/05/2017

Transferred to new eviQ website. Protocol version number increased to V.3.
Link to the independent evaluation of the evidence completed in 2006/7 removed from the evidence section as no longer relevant.

Antiemetic change: Netupitant/palonosetron combination has replaced aprepitant and a 5HT3 receptor antagonist in combination with dexamethasone for all highly emetogenic regimens.

10/05/2018

Haematological dose modifications updated per consensus of the expert clinician group. Version number increased to V.4.

22/06/2018

Antiemetics updated to be in line with international guidelines. Note to dexamethasone added.

The information contained in this protocol is based on the highest level of available evidence and consensus of the eviQ reference committee regarding their views of currently accepted approaches to treatment. Any clinician (medical oncologist, haematologist, radiation oncologist, medical physicist, radiation therapist, pharmacist or nurse) seeking to apply or consult this protocol is expected to use independent clinical judgement in the context of individual clinical circumstances to determine any patient's care or treatment. Use is subject to eviQ’s disclaimer available at www.eviQ.org.au